DZ2002 is a reversible inhibitor of S-Adenosyl-L-homocysteine hydrolase (SAHH). It has been demonstrated that DZ2002 selectively suppresses macrophage function and activates B cells function, inhibits cell immune and humoral immune responses, and has a wide margin between the toxic and therapeutic doses with a high therapeutic index (Chong-Sheng Yuan, USP: 2005/0182075, 2005; Yun-Feng Fu, Jun-Xia Wang, Jian-Ping Zuo etc., The Journal of Pharmacology and Experimental Therapeutics, 118, 1229˜1237; Brian R. Lawson, Yulia Manenkova, Chong Yuan etc., The Journal of Immunology, 178, 5366˜5374, 2007).
A known method for preparing DZ2002 started from (S)-(−)-α-hydroxybutyrolactone, after the hydroxyl group had been protected with a silyl group, the lactone was treated with tetraisopropyl titanate to open the lactone ring, followed by being converted to a corresponding p-toluenesulfonate. Then it was nucleophilically substituted with adenine and deprotected by removal of the silyl protective group to obtain DZ2002. The details are shown in Scheme 1. In the preparation method, (S)-(−)-α-hydroxybutyrolactone is expensive, the ring-opening reaction using tetraisopropyl titanate has a low yield with a complicated post-treatment, and the chiral center tends to be racemized during the reaction. In addition, DZ2002 is purified by column chromatography, which is time-consuming with a low productivity.
